NFkappaB activation is required for the neuroprotective effects of pigment epithelium-derived factor (PEDF) on cerebellar granule neurons - PubMed (original) (raw)
. 2001 Nov 16;276(46):43313-9.
doi: 10.1074/jbc.M107831200. Epub 2001 Sep 11.
Affiliations
- PMID: 11553640
- DOI: 10.1074/jbc.M107831200
Free article
NFkappaB activation is required for the neuroprotective effects of pigment epithelium-derived factor (PEDF) on cerebellar granule neurons
T Yabe et al. J Biol Chem. 2001.
Free article
Abstract
Pigment epithelium-derived factor (PEDF) protects immature cerebellar granule cells (1-3 days in vitro) against induced apoptosis and mature cells (5+ days in vitro) against glutamate toxicity, but its precise mechanism is still unknown. Because the transcription factor NFkappaB blocks cell death, including neuronal apoptosis, we have investigated the ability of PEDF to exert its effects via NFkappaB activation. PEDF induced an increased phosphorylation of IkappaBalpha, decreased levels of IkappaB proteins, and translocation of p65 (RelA) to the nucleus followed by a time-dependent increase of NFkappaB-DNA binding activity in both immature and mature neurons. The protective effects of PEDF against both induced apoptosis and glutamate toxicity were blocked by the addition of either the IkappaB kinase inhibitor BAY 11-7082, which inhibits the phosphorylation of IkappaB, or N-acetyl-Leu-Leu-norleucinal, which blocks proteosome degradation of IkappaB, demonstrating that NFkappaB is required for the neuroprotective effects of PEDF. Reverse transcription-polymerase chain reaction analysis revealed that up-regulation of the anti-apoptotic genes for Bcl-2, Bcl-x, and manganese superoxide dismutase was observed in PEDF-treated immature but not mature neurons. Up-regulation of nerve growth factor, brain-derived neurotrophic factor, and glial cell-derived neurotrophic factor mRNA was long-lasting in mature neurons. These results suggest that PEDF promotes neuronal survival through activation of NFkappaB, which in turn induces expression of anti-apoptotic and/or neurotrophic factor genes.
Similar articles
- Pigment epithelium-derived factor (PEDF) differentially protects immature but not mature cerebellar granule cells against apoptotic cell death.
Araki T, Taniwaki T, Becerra SP, Chader GJ, Schwartz JP. Araki T, et al. J Neurosci Res. 1998 Jul 1;53(1):7-15. doi: 10.1002/(SICI)1097-4547(19980701)53:1<7::AID-JNR2>3.0.CO;2-F. J Neurosci Res. 1998. PMID: 9670988 - [PEDF: an endogenous factor displaying potent neuroprotective, neurotrophic, and antiangiogenic activity].
Marciniak K, Butwicka A, Nowak JZ. Marciniak K, et al. Postepy Hig Med Dosw (Online). 2006;60:387-96. Postepy Hig Med Dosw (Online). 2006. PMID: 16885909 Review. Polish. - Unique aspects of transcriptional regulation in neurons--nuances in NFkappaB and Sp1-related factors.
Mao XR, Moerman-Herzog AM, Chen Y, Barger SW. Mao XR, et al. J Neuroinflammation. 2009 May 18;6:16. doi: 10.1186/1742-2094-6-16. J Neuroinflammation. 2009. PMID: 19450264 Free PMC article. Review.
Cited by
- Pigment Epithelium-Derived Factor (PEDF) Receptors Are Involved in Survival of Retinal Neurons.
Bürger S, Meng J, Zwanzig A, Beck M, Pankonin M, Wiedemann P, Eichler W, Unterlauft JD. Bürger S, et al. Int J Mol Sci. 2020 Dec 31;22(1):369. doi: 10.3390/ijms22010369. Int J Mol Sci. 2020. PMID: 33396450 Free PMC article. - Pigment Epithelium-Derived Factor Improves Paracellular Blood-Brain Barrier Integrity in the Normal and Ischemic Mouse Brain.
Riabinska A, Zille M, Terzi MY, Cordell R, Nieminen-Kelhä M, Klohs J, Piña AL. Riabinska A, et al. Cell Mol Neurobiol. 2020 Jul;40(5):751-764. doi: 10.1007/s10571-019-00770-9. Epub 2019 Dec 20. Cell Mol Neurobiol. 2020. PMID: 31858356 - NF-κB Activation Promotes Alphavirus Replication in Mature Neurons.
Yeh JX, Park E, Schultz KLW, Griffin DE. Yeh JX, et al. J Virol. 2019 Nov 26;93(24):e01071-19. doi: 10.1128/JVI.01071-19. Print 2019 Dec 15. J Virol. 2019. PMID: 31554691 Free PMC article. - Cellular Specificity of NF-κB Function in the Nervous System.
Dresselhaus EC, Meffert MK. Dresselhaus EC, et al. Front Immunol. 2019 May 9;10:1043. doi: 10.3389/fimmu.2019.01043. eCollection 2019. Front Immunol. 2019. PMID: 31143184 Free PMC article. Review. - Pigment Epithelium-Derived Factor Promotes Axon Regeneration and Functional Recovery After Spinal Cord Injury.
Stevens AR, Ahmed U, Vigneswara V, Ahmed Z. Stevens AR, et al. Mol Neurobiol. 2019 Nov;56(11):7490-7507. doi: 10.1007/s12035-019-1614-2. Epub 2019 May 2. Mol Neurobiol. 2019. PMID: 31049830 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous